FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis

被引:126
|
作者
Lachowski, Dariusz [1 ]
Cortes, Ernesto [1 ]
Robinson, Benjamin [1 ]
Rice, Alistair [1 ]
Rombouts, Krista [2 ]
Hernandez, Armando E. Del Rio [1 ]
机构
[1] Imperial Coll London, Dept Bioengn, Cellular & Mol Biomech Lab, London SW7 2AZ, England
[2] UCL, Inst Liver & Digest Hlth, Royal Free Hosp, Regenerat Med & Fibrosis Grp, London NW3 2PF, England
来源
FASEB JOURNAL | 2018年 / 32卷 / 02期
基金
欧洲研究理事会;
关键词
mechanotransduction; focal adhesions; directed migration; FOCAL ADHESION KINASE; MATRIX STIFFNESS; PATHWAY; YAP/TAZ; CELLS; MECHANOTRANSDUCERS; HOMEOSTASIS; CARCINOMA; RIGIDITY; SIZE;
D O I
10.1096/fj.201700721R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates fundamental processes in cells such as growth, survival, and migration. FAK is one of the first molecules recruited to focal adhesions in response to external mechanical stimuli and therefore is a pivotal mediator of cell mechanosignaling, and relays these stimuli to other mechanotransducers within the cytoplasm. Yes-associated protein (YAP) has been identified recently as one of these core mechanotransducers. YAP translocates to the nucleus following changes in cell mechanics to promote the expression of genes implicated in motility, apoptosis, proliferation, and organ growth. Here, we show that FAK controls the nuclear translocation and activation of YAP in response to mechanical activation and submit that the YAP-dependent process of durotaxis requires a cell with an asymmetric distribution of active and inactive FAK molecules.
引用
收藏
页码:1099 / 1107
页数:9
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